title: Evolutionary dynamics of bovine coronaviruses: natural selection pattern of the spike gene implies adaptive evolution of the strains.
abstract: Coronaviruses demonstrate great potential for interspecies transmission, including zoonotic outbreaks. Although bovine coronavirus (BCoV) strains are frequently circulating in cattle farms worldwide, causing both enteric and respiratory disease, little is known about their genomic evolution. We sequenced and analysed the full-length spike (S) protein gene of 33 BCoV strains from dairy and feedlot farms collected during outbreaks that occurred from 2002 to 2010 in Sweden and Denmark. Amino acid identities were >97 % for the BCoV strains analysed in this work. These strains formed a clade together with Italian BCoV strains and were highly similar to human enteric coronavirus HECV-4408/US/94. A high similarity was observed between BCoV, canine respiratory coronavirus (CRCoV) and human coronavirus OC43 (HCoV-OC43). Molecular clock analysis of the S gene sequences estimated BCoV and CRCoV diverged from a common ancestor in 1951, while the time of divergence from a common ancestor of BCoV and HCoV-OC43 was estimated to be 1899. BCoV strains showed the lowest similarity to equine coronavirus, placing the date of divergence at the end of the eighteenth century. Two strongly positive selection sites were detected along the receptor-binding subunit of the S protein gene: spanning amino acid residues 109-131 and 495-527. By contrast, the fusion subunit was observed to be under negative selection. The selection pattern along the S glycoprotein implies adaptive evolution of BCoVs, suggesting a successful mechanism for BCoV to continuously circulate among cattle and other ruminants without disappearance.
authors.affiliation: Division of Ruminant Medicine and Veterinary Epidemiology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Mehdi R M
authors.initials: MRM
authors.lastname: Bidokhti
authors.affiliation: Division of Ruminant Medicine and Veterinary Epidemiology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Tråvén
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, USA.
authors.forename: Neel K
authors.initials: NK
authors.lastname: Krishna
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.|Department of Virology, Immunobiology and Parasitology, National Veterinary Institute, Box 7028, SE-751 89 Uppsala, Sweden.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Munir
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.|Department of Virology, Immunobiology and Parasitology, National Veterinary Institute, Box 7028, SE-751 89 Uppsala, Sweden.
authors.forename: Sándor
authors.initials: S
authors.lastname: Belák
authors.affiliation: Division of Ruminant Medicine and Veterinary Epidemiology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Alenius
authors.affiliation: Department of Immunology, The Pirbright Institute, Ash Road, Pirbright GU24 0NF, UK.
authors.forename: Martí
authors.initials: M
authors.lastname: Cortey
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000821:virology; D016000:Cluster Analysis; D018352:Coronavirus Infections / Q000662:veterinary / Q000821:virology; D017938:Coronavirus, Bovine / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D003718:Denmark / Q000453:epidemiology; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D064370:Spike Glycoprotein, Coronavirus; D013548:Sweden / Q000453:epidemiology; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D012367:RNA, Viral; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus